Abstract
Developmental transitions of germ cells are often regulated at the level of post-transcriptional control of gene expression. In the Caenorhabditis elegans germline, stem and progenitor cells exit the proliferative phase and enter meiotic differentiation to form gametes essential for fertility. The RNA binding protein GLD-1 is a cell fate regulator that promotes meiosis and germ cell differentiation during development by binding to and repressing translation of target messenger RNAs. Here, we discovered that some GLD-1 functions are promoted by binding to DLC-1, a small protein that functions as an allosteric regulator of multisubunit protein complexes. We found that DLC-1 is required to regulate a subset of GLD-1 target messenger RNAs and that DLC-1 binding GLD-1 prevents ectopic germ cell proliferation and facilitates gametogenesis in vivo. Additionally, our results reveal a new requirement for GLD-1 in the events of oogenesis leading to ovulation. DLC-1 contributes to GLD-1 function independent of its role as a light chain component of the dynein motor. Instead, we propose that DLC-1 promotes assembly of GLD-1 with other binding partners, which facilitates formation of regulatory ribonucleoprotein complexes and may direct GLD-1 target messenger RNA selectivity.
| Original language | English |
|---|---|
| Pages (from-to) | 665-681 |
| Number of pages | 17 |
| Journal | Genetics |
| Volume | 211 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2019 |
Funding
We thank the members of Voronina laboratory for helpful discussions. Several nematode strains were provided by Caenorhabditis Genetics Center, funded by the National Institutes of Health (NIH) (grant P40OD010440). The K76, anti-MSP, and anti-MY0-3 antibodies were obtained from the Developmental Studies Hybridoma Bank (National Institute of Child Health and Human Development, The University of Iowa). The anti-GLD-1 antibody was a gift from Tim Schedl. Confocal microscopy was performed in the University of Montana BioSpectroscopy Core Research Laboratory, which is operated with support from NIH Center of Biomedical Research Excellence Award P20GM103546 to the Center for Biomolecular Structure and Dynamics and from the Vice President of Research and Creative Scholarship at the University of Montana, and the S10OD021806 NIH award for acquisition of confocal microscope. This work was supported by the NIH grant GM109053 to E.V., a University of Montana Research Award to M.E., and a University of Montana Undergraduate Research Award to E.O.
| Funder number |
|---|
| P20GM103546, P40OD010440 |
| R01GM109053 |
Keywords
- Germline
- Post-transcriptional regulation
- RNA binding protein
- Tumor